X-linked adrenoleukodystrophy is a neurodegenerative disorder that is characterized by both an aggressive cerebral form that suddenly strikes in childhood and by a milder adult form that presents primarily as a distal axonopathy. The primary genetic defect is identical in both forms and it has a frequency of 1:21,000 males. All patients with the disorder have elevated levels of levels of very long chain fatty acids. The purpose of this study is to develop a newborn screening assay to detect the disorder. Early identification of the patients will allow them to be treated and will enable patients with the severe cerebral form to either avoid it or delay its progression. Because total very long chain fatty acid analysis has inherent contamination problems, this study will take the novel approach of determining fatty acid changes in one lipid fraction, sphingomyelin. The first aim will focus on developing and optimizing a tandem mass spectrometry assay for sphingomyelins. The second aim will focus on its application to whole blood samples. Finally, the last aim will aim at differentiating normal individuals from X-linked adrenoleukodystrophy patients. The proposed approach of sampling from a large lipid pool represents a new means to study diseases.